Crystal structure and Hirshfeld surface analysis of 7-ethoxy-5-methyl-2-(pyridin-3-yl)-11,12-dihydro-5,11-methano[1,2,4]triazolo[1,5-c][1,3,5]benzoxadiazocine

In the crystal, N—H⋯N hydrogen bonds link the molecules into the supramolecular chains propagating along the c-axis direction.

The title compound, C 19 H 19 N 5 O 2 , was prepared by the reaction of 3-amino-5-(pyridin-3-yl)-1,2,4-triazole with acetone and 2-hydroxy-3-ethoxybenzaldehyde. It crystallizes from ethanol in a tetragonal space group, with one molecule in the asymmetric unit. The 1,2,4-triazole five-membered ring is planar (maximum deviation = 0.0028 Å ). The pyridine and phenyl rings are also planar with maximum deviations of 0.0091 and 0.0094 Å , respectively. In the crystal, N-HÁ Á ÁN hydrogen bonds link the molecules into supramolecular chains propagating along the c-axis direction. Hirshfeld surface analysis and twodimensional fingerprint plots have been used to analyse the intermolecular interactions present in the crystal.

Chemical context
The title compound represents a conformationally restricted analogue of so-called Biginelli compounds known to exhibit multiple pharmacological activities. It was selected for a single-crystal X-ray analysis in order to probe the chemical and spatial requirements of some kinds of activity. 4-Aryl-3,4dihydropyrimidine-2(1H)-ones and -thiones, known as Biginelli compounds, display a wide spectrum of significant pharmacological activities (Kappe, 2000). For example, these pyrimidine derivatives were assayed as antihypertensive agents, selective 1a -adrenergic receptor antagonists, neuropeptide Y antagonists and were used as a lead for the development of anticancer drugs (Kappe, 2000). The Biginelli products have also been found to be potent hepatitis B replication inhibitors (Deres et al., 2003).
Recently, the ability of oxygen-bridged azolopyrimidine derivatives to inhibit Eg5 activity has been examined (Svetlík et al., 2010). As each of the above activities originates from stereo-selective binding of the drug molecule to its specific receptor, it is of interest to design a conformationally restricted probe molecule in order to examine geometric requirements of the given receptor binding site.

Supramolecular features
In the crystal, the N-HÁ Á ÁN hydrogen bonds link the molecules, forming the supramolecular chains propagating along the c-axis direction (Table 1, Fig. 2).

Hirshfeld surface analysis
Crystal Explorer17.5 (Turner et al., 2017) was used to analyse the interactions in the crystal; fingerprint plots mapped over d norm (Figs. 3 and 4) were generated. The molecular Hirshfeld surfaces were obtained using a standard (high) surface resolution with the three-dimentional d norm surfaces mapped over a fixed colour scale of À0.484 (red) to 1.652 (blue). There are two red spots in the d norm surface (Fig. 3), which are on the Nacceptor atoms involved in the interactions listed in Table 1. The red spots indicate the regions of donor-acceptor interactions (Kansiz et al., 2018;Ş en et al., 2017a,b, 2018Yaman et al., 2018).
The intermolecular interactions of the title compound are shown in the 2D fingerprint plots shown in Fig Table 1 Hydrogen-bond geometry (Å , ).

Figure 2
A partial view of the crystal packing of the title compound. Dashed lines denote the intermolecular N-HÁ Á ÁN hydrogen bonds.

Figure 1
The molecular structure of the title compound, showing the atom labelling. Displacement ellipsoids are drawn at the 30% probability level.

Figure 3
The Hirshfeld surface of C 19 H 19 N 5 O 2 mapped with d norm .
two-dimensional fingerprint plots with a contribution to the overall Hirshfeld surface of 52.6% (Fig. 6). The contribution from the NÁ Á ÁH/HÁ Á ÁN contacts, corresponding to the N-HÁ Á ÁN interaction, is represented by a pair of sharp spikes characteristic of a strong hydrogen-bond interaction (16.3%). The whole fingerprint region and all other interactions, which are a combination of d e and d i , are displayed in Fig. 6.

Synthesis and crystallization
The synthesis of the title compound (    mixed in a microwave process vial, and then a 4 N solution of HCl in dioxane (0.07 mL, 0.3 mmol) was added. The mixture was irradiated at 423 K for 30 min. The reaction mixture was cooled by an air flow and stirred for 24 h at room temperature for complete precipitation of the product. The precipitate was filtered off, washed with EtOH (1.0 mL) and Et 2 O (3 Â 1.0 mL), and dried. Compound (I) was obtained in the form of a white solid. It was recrystallized from ethanol.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refined as a 2-component inversion twin.